DESCRIPTION (Adapted from the Applicant's Description) This application is for a Midcareer Investigator Award in Patient-Oriented Research for Silva Arsianian, M.D., Associate Professor of Pediatrics University of Pittsburgh, Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children s Hospital of Pittsburgh. The award will serve two purposes: (1) to assist the principal investigator to further develop her research endeavors in investigating insulin resistance in childhood; and (2) more importantly, to provide her with protected time to mentor the future generation of clinician- scientists in patient-oriented research (POR) by providing state-of-the-art clinical research in the multiple aspects of pediatric metabolism and diabetes. Cardiovascular disease is the leading cause of death in the United States. A growing body of evidence points to insulin resistance and the cardiovascular dysmetabolic syndrome (hyperglycemia, hyperinsulinemia, hyperlipidemia and hypertension) as a major risk factor. Dr. Arsianian's research has focused on investigating insulin resistance in childhood with the objective of early intervention/prevention to improve overall health outcome in adulthood. The principal investigator's POR is to investigate hormonal, metabolic, nutritional and environmental causes of insulin resistance in children. For the K24 award the focus of research will be: (1) to continue to investigate racial (Black/White) differences in insulin sensitivity and metabolic partitioning of fat in an effort to determine childhood risk factors for the higher rates of obesity, Type 2 diabetes and CVD in African-Americans; (2) to assess, longitudinally, the effects of dihydrotestosterone (DHT), a nonaromatizable androgen in prepubertal boys to determine the role of androgen vs growth hormone in insulin resistance of puberty; and (3) to investigate the relationship of hyperinsulinemia and hyperandrogenenua, cross-sectionally and longitudinally, in female children with hyperandrogenisnt The clinical research tools include insulin-glucose clamp experiments, stable isotope methodologies, indirect calorimetry, assessment of body composition and body fat topography, assessment of physical fitness and activity and assessment of free-living energy expenditure. Future directions in POR include: (1) Family- based behavioral lifestyle treatment of pediatric obesity; (2) multi center investigation of the emerging epidemic of obesity-related Type 2 diabetes in children, especially African-American and Latino; (3) development of noninvasive methods, p31 NMR spectroscopy to study muscle energy metabolism in children; (4) intervention/prevention strategies for childhood obesity. Early identification in childhood of precursors of adult morbidity will form the basis to fulfill the objectives of "Healthy People 2000." The mentoring component of this award will insure that the new generation of clinician- scientists will be fully prepared for an academic/investigative career in POR in pediatrics to carry to the next millennium